The human immunodeficiency virus HIV-1 is characterized by a very high mutation frequency. Because the virus mutates so frequently, drug resistance to antiviral therapies s is an ongoing challenge. Common regimens of anti-HIV drugs include Nucleoside Reverse Transcriptase Inhibitors (NRTIs) that mimic thymidine (AZT, stavudine), deoxycytidine (Lamivudine, Emtricitabine) or deoxyguanosine (Abacavir) nucleosides.
Acyclovir (ACV) is a deoxyguanosine analogue particularly active against α-herpesiviruses HHV-1, HHV-2, and HHV-3 (respectively known as herpes simplex viruses 1 and 2 and varicella zoster virus). ACV is phosphorylated in herpesvirus-infected cells by a viral kinase. The resulting monophosphate is then converted into ACV triphosphate (ACV-TP) by cellular enzymes and is subsequently incorporated in the nascent viral DNA chain, causing its obligate termination. Moreover, the incorporated ACV-TP causes the viral DNA polymerase to become irreversibly bound to the terminated chain.